This renewal proposal describes plans to continue Cornell's Molecular Biophysics Training Grant Program, which offers vigorous interdisciplinary training that combines physical and biological sciences. The program, now in its 23rd year, further advances the training of our most motivated and well-qualified students by focusing their graduate academic work around a core curriculum in areas spanning both physical and biological disciplines. The trainees selected to participate may have undergraduate degrees in either physical or biological sciences and must have been admitted to the Graduate School at Cornell for training leading to the Ph.D. in one of the Graduate Fields of the twenty-eight participating faculty spanning eight departments, seventeen fields, and three Colleges. All participating faculty are associated with Cornell's well established and continuously growing Biophysics Program, and have well- funded quality research programs either in physics with strong biological applications or in biology with strong physical connections. The overall research interests of the faculty are broadly distributed and include: the investigation of structue and function of proteins and other macromolecules using theoretical approaches; structure determination by synchrotron X- ray crystallography; electron spin resonance spectroscopy and multidimensional NMR; single molecule studies of dynamics of molecular motors; structures and molecular mechanisms of cell membranes, receptors, and neurotransmitters and associated cellular functions; materials and technology developments including nonlinear laser microscopy, steady-state and time resolved spectroscopy and imaging, single channel recording, optical tweezers, and nanofabrication. Through collaborations and University center facilities, Cornell offers a natural fertile ground for innovation and creative research ideas. The program supports 12 trainees each year, with a total duration of support for each individual at 2-3 years. Trainees undertake interdisciplinary studies with advanced courses in mathematics, quantum mechanics, statistical thermodynamics, biochemistry, molecular and cell biology, computation and instrumentation, and other special topics. In addition, students participate in multiple program functions including a weekly Biophysics Colloquium, a student and faculty retreat, and Summer Student Seminars. These activities serve to provide continuity and program identity within the far- reaching interdisciplinary structure of the program. Thesis research and collaborations in the laboratories of the participating faculty complete preparation for a career of teaching and research in molecular biophysics. Through these experiences, they gain exposure to, and experience in, interdisciplinary biomedical research. PUBLIC HEALTH RELEVANCE: The diagnosis and treatment of disease increasingly relies on the understanding of macromolecular structures and molecular mechanisms that underlie medical conditions and the development of new techniques pertinent to important issues in public health. The goal of this program is to train students to apply the powerful techniques of physics and chemistry to problems of medical significance. This will lead to the design of new drug therapies, the identification of new cellular and molecular targets for said therapy, a better understanding of the cell components involved in diseases, and new, particularly noninvasive, diagnostic procedures.